Investigation of miscibility estimation methods between indomethacin and poly(vinylpyrrolidone-co-vinyl acetate)

The investigation of the miscibility between active pharmaceutical ingredients (API's) and polymeric excipients is of great interest for the formulation and development of amorphous solid dispersions, especially in the context of the prediction of the stability of these systems. Two different methods were applied to determine the miscibility between model compounds poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) and indomethacin (IND), viz. the measurement of the glass transition temperature (T_g) and the melting point depression method framed on the Flory-Huggins theory. Measurement of the glass transition temperatures of the binary blends showed the formation of an amorphous single phase system between the PVPVA and the IND regardless of the composition. Variation of T_g with the composition was well described by the Gordon-Taylor equation leading to the error of concluding lack of intermolecular interactions between the materials. Application of the Brostow-Chiu-Kalogeras-Vassilikou-Dova (BCKV) model shows a negative interaction parameter (a₀) suggesting the presence of drug-drug intermolecular interactions. Application of the melting point depression method within the framework of the Flory-Huggins theory proved the miscibility of the system at temperatures close to the melting point of IND.